Thyroid Hormone Level May Signal Mortality Risk

Action Points

Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Note that this cohort study demonstrated an association between higher free T4 levels (but not TSH levels) and all-cause mortality in men without thyroid disease.

Be aware that the routine evaluation of thyroid function in asymptomatic men is not recommended by any major societies.

SAN FRANCISCO -- Levels of free thyroxine at the higher end of the normal range are associated with all-cause mortality in older men who do not have thyroid disease, researchers found.

Compared with men in the lowest quartile of free thyroxine levels (9.64 to 14.46 pmol/L), those in the highest quartile (17.32 to 25.04 pmol/L) were more likely to die over an average of 6.4 years of follow-up (HR 1.20, 95% CI 1.03 to 1.41), according to Bu Beng Yeap, MBBS, PhD, of the University of Western Australia in Perth.

The findings were similar when men with subclinical hyper- or hypothyroidism were excluded (HR 1.20, 95% CI 1.02 to 1.42), he reported at the Endocrine Society meeting here.

Further research is needed to determine whether the relationship is causal, but high-normal free thyroxine levels should probably prompt a closer look at that patient, Yeap said in an interview with MedPage Today.

"If you have an older man and for whatever reason you've checked his thyroid function, if he has a normal thyroid stimulating hormone level but his free thyroxine level is in the higher end of the normal range, that's probably when you should look to see if this man has any other risk factors for cardiovascular disease and mortality that you can address," he said.

Both overt thyroid disease and subclinical thyroid dysfunction have been tied to worse outcomes, but the researchers wanted to explore whether similar relationships between thyroid hormones and outcomes were seen in euthyroid men.

Yeap and colleagues examined data from the Health in Men study, which included men ages 70 to 89 who were living in Perth. The researchers excluded men with known thyroid disease, leaving 3,885 for the current analysis.

Follow-up lasted for up to 9 years, and during that time 21.5% of the men died. At baseline, those who died during the study were about 2 years older (78.5 versus 76.6, P<0.001) and had a significantly higher average free thyroxine level (16.2 versus 15.8 pmol/L, P<0.001).

After adjustment for age, smoking, body mass index, waist-to-hip ratio, blood pressure, lipids, creatinine, and comorbidities, higher free thyroxine levels -- but not levels of thyrotropin -- were significantly associated with an increased risk of death from any cause.

Yeap cautioned that the observational design of the study does not allow for conclusions to be made about causality. It could be, he said, that free thyroxine is simply a marker of some other factor that is increasing the risk of death.

If there is a causal relationship, however, it would likely involve the adverse cardiovascular effects of a higher level of free thyroxine, he said, adding that effects on other body systems cannot be ruled out considering previously observed relationships between mildly elevated free thyroxine levels and frailty and dementia.

Yeap is the recipient of a Clinical Investigator Award from the Sylvia and Charles Viertel Charitable Foundation. Hormone assays were funded by research grants from the Fremantle Hospital Medical Research Foundation and the Ada Bartholomew Medical Research Trust. The Health In Men Study was funded by project grants from the National Health and Medical Research Council of Australia. Roche Diagnostics supplied assay reagents for the study.

Yeap did not report any conflicts of interest.

Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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